LSUHSC COBRE: REPLICATION OF MURINE NOROVIRUS 1, MNV-1

这个子项目是许多利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 项目4：鼠诺如病毒1型（MNV-1）复制 项目PI：Stephanie M. Karst博士 诺如病毒是引起全球95%非细菌性流行性胃肠炎的重要病原体。 然而，由于缺乏组织培养和小动物模型系统，它们一直很难研究。 我们在免疫缺陷小鼠集落中发现了鼠诺如病毒MNV-1，并表明其在组织培养中有效感染巨噬细胞和树突状细胞。 我们正在研究干扰素（IFN）信号传导保护免受MNV-1诱导的疾病的机制。 研究方法：将正常小鼠的感染与IFN信号传导的特定组分缺陷的小鼠的感染进行比较，以确定IFN在体内MNV-1保护中所起的作用。 比较存在或不存在IFN处理的容许细胞的感染使我们能够研究IFN信号传导抑制MNV-1复制的分子机制。 结果如下：我们已经确定，IFN信号可以阻止MNV-1在肠道中的复制，控制病毒扩散到外周组织，并保护细胞免于体内凋亡。 我们还确定IFN在病毒翻译之前的复制周期的非常早期的步骤阻断MNV-1复制。 讨论内容：人类诺如病毒感染导致衰弱性疾病，但很快就解决了，这表明先天免疫反应的组分在诺如病毒保护中至关重要。 由于长期免疫被认为不会在诺如病毒感染后发展，因此了解对感染的先天免疫应答对于开发合理的治疗方案至关重要。因此，IFN信号传导在保护免受诺如病毒感染中所起作用的机制研究将为未来的翻译设计奠定基础。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Project 4: Replication of murine norovirus 1, MNV-1 Project PI: Stephanie M. Karst, Ph.D. Introduction: Human noroviruses are important pathogens responsible for 95% of non-bacterial epidemic gastroenteritis worldwide. However, they have been very difficult to study due to a lack of tissue culture and small animal model systems. We discovered murine norovirus, MNV-1, in immunodeficient mouse colonies and have shown that it productively infects both macrophages and dendritic cells in tissue culture. We are investigating the mechanism(s) by which interferon (IFN) signaling protects from MNV-1 induced disease. Methods: Infection of normal mice is compared to infection of mice deficient in specific components of IFN signaling to determine the role that IFN plays in MNV-1 protection in vivo. Comparing infection of permissive cells in the presence or absence of IFN treatment allows us to investigate the molecular mechanism(s) by which IFN signaling inhibits MNV-1 replication. Results: We have determined that IFN signaling prevents replication of MNV-1 in the intestine, controls virus spread to peripheral tissues, and protects cells from apoptosis in vivo. We have also determined that IFN blocks MNV-1 replication at a very early step in the replication cycle preceding viral translation. Discussion: Human norovirus infection causes debilitating disease but is resolved rapidly, suggesting that components of the innate immune response are critical in norovirus protection. Because long-term immunity is not thought to develop upon norovirus infection, understanding the innate immune responses to infection is critical for developing rational treatment regimes. Thus, mechanistic studies of the role(s) played by IFN signaling in protection from norovirus infection will lay the foundation for future translational designs.